Biochemistry for Nursery Students 2024-2025 PDF

1 2024-2025  2 Contents Subject Page Carbohydrate metabolism 3 Lipid metabolism 19 Protein metabolism 29 Vitamin 41 Minerals metabolism 51 Body fluid 58 Enzymes 65...

1 2024-2025  2 Contents Subject Page Carbohydrate metabolism 3 Lipid metabolism 19 Protein metabolism 29 Vitamin 41 Minerals metabolism 51 Body fluid 58 Enzymes 65  3 Carbohydrate metabolism  4 Digestion of carbohydrate In mouth (Salivary amylase) Act on cooked starch and glycogen converting it into dextrin, maltose, iso maltose, some starch remain undigested Pancreatic amylase Act at pH 7.1 Act on cooked and uncooked starch converting it into maltose, iso maltose, Final digestion by intestinal enzyme Lactose lactase glucose + galactose Maltose maltase 2 α glucose Sucrose sucrase glucose + Fructose Isomaltose dexstrinase 2 α glucose (bond between I, 6 carbon) Digestion of cellulose Cellulose not digested due to absence of enzyme cellulase that attack β linkage Used in treatment of constipation Fate of absorbed sugar 1- Uptake by tissues Uptake by liver where galactose & fructose converted to glucoes 2- Utilization by tissues A- Oxidation 1- Major pathway : glycolysis & krebs for production of energy 2- HMP (hexose mono phosphate) shunt: give ribose , NADP 3- Production of glucouronic acid has role in heparin synthesis B- Storage Glycogen: by glycogenesis Fat : lipogenesis C- Conversion Ribose, deoxyribose DNA, RNA Lactose milk  5 Energy (ATP) NADPH Glycogen glycolysis & krebs HMP shunt storage Lipogenesis Glucose Ribose , deoxyribose RNA DNA Lactose (Milk sugar) in mammary gland Glucose oxidation All carbohydrate cycle occur in cytoplasm except krebs occur in mitochondria Complete oxidation of glucose to CO2 + H2O occur part in cytoplasm (glycolysis) and part in mitochondria (Krebs) major pathway Mitochondria are absent in RBC or where there O2 lack during muscular exercise  6 Cytoplasmic pathway for glucose oxidation Glycolysis (Anarobic phase of glucose oxidation ) Embden –Meyerohf pathway Means oxidation of glucose into pyruvate Site: Cytoplasm of all tissues but important in 1- Muscle during exercise due to O2 lack 2- RBC due to absence of mitochondria Function of glycolysis 1- Energy production It is the only sources of energy to the muscle during contraction and to RBC due to absence of mitochondria It gives 8 or 6 ATP in presence of O2 2- Give 2,3 bishosphoglycerate (BPG) which decrease affinity of Hb to O2 so O2 go easy to tissues 3- It gives pyruvic acid that can begin krebs cycle 4- DHAP can converted to glycerol-3 -phosphate which important for lipogenesis 5- Gives 2 AA A- Serine derived from 3 phsphoglycerate B- Alanine derived from pyruvic acid Mitochondrial pathway for glucose oxidation Complete oxidation of glucose to CO2 + H2O occur part in cytoplasm (glycolysis) and part in mitochondria (Krebs) major pathway First stage : Oxidative decarboxylation of pyruvate to acetyl CoA Second stage: Krebs cycle Ex. For Oxidative decarboxylation 1- Conversion of pyruvate to acetyl CoA (active acetate) 2- Conversion of α ketoglutarate to succinyl CoA (active succinate)  7 Oxidative decarboxylation of pyruvate to acetyl CoA Catalyzed by different enzyme called pyruvate dehydrogenase complex (PDC) Or (PDH) This require 5 coenzyme 1- TPP coenzyme of Vit. B1 2- Lipoic acid : 2 form present reduced and oxidized 3- CoASH: coenzyme of pantothenic 4- FAD: coenzyme of Vit. B2 (riboflavin) 5- NAD: coenzyme of Vit. Niacin CH3-CO-COOH pyruvate dehydrogenase complex CH3-CO~ScoA Pyruvate TPP, Lipoic, FAD Acetyl-CoA NAD CoASH NADH2+ CO2  8 Citric acid cycle (CAC) Krebs cycle or Tricarboxylic acid cycle (TCA) Aeropic phase of glucose oxidation Mitochondrial phase of glucose oxidation Hans krebs discover the cycle in 1935 and complete it at 1940 Site: Mitochondria Function of krebs (Amphibolic role) Amphibolic means anabolic and catabolic 1- Catabolic role A- Production of energy 12 ATP B- Krebs used for complete oxidation of carbohydrate , lipid , protein 2- Anabolic role A- Synthesis of heme : by succinyl CoA + glycine B- AA synthesis 1- Glutamic transamination -ketoglutarate GPT 2- Aspartic transamination oxaloacetate GOT C- Synthesis of fatty acid Mitochondria Cytoplasm Acetyl CoA + oxaloacetate Citrate Citrate Acetyl CoA + oxaloacetate Synthesis of fatty acid D- Gluconeogenesis Gluconeogenesis is synthesis of glucose from non carbohydrate source require krebs cycle E- Importance of CO2 1- Pyruvate + CO2 oxaloacetate 2- Acetyl CoA+ CO2 Malonyl CoA (Synthesis of fatty acid) 3- NH3 + CO2 carbamoyl phosphate (Synthesis of urea)  9 Hexose mono phosphate shunt (HMP shunt) Pentose shunt Site: occur in cytoplasm of liver Function of HMP shunt 1-Production of pentoses pentoses are important in synthesis of DNA , RNA 3- Production of NADPH+H which important in A- Synthesis of fatty acid, cholesterol B- Synthesis of sphingosine, galactolipid C- Synthesis of glucouronic acid D- Synthesis of non essential AA E- Reduction of glutathione which important for 1-Keep cell membrane intact by convert H2O2 to H2O 2-Protect lipid against auto-oxidation 3-Has role in AA absorption 4-Inactivate insulin hormone F- NADPH+H act as coenzyme for cytochrome P 450 Which important to covert toxic drug or compound to non toxic RH (toxic) cytochrome P 450 ROH (non toxic) NADPH2 O2 NADP H2O  11 Favism Definition Its deficiency in glucose -6- P dehydrogenase (G6PD) lead to hemolysis of RBC especially after intake of fava beans Mechanism G-6-P G6PD 6 phosphogluconolactone NADP NADPH2 Oxidized glutathione reductase reduced glutathione NADPH2 NADP Reduced glutathione + H2O2 perxidase 2H2O + Oxidized glutathione So ↓ G6PD ↓ NADPH2 ↓ reduced glutathione ↑ H2O2 ↑ hemolysis in RBC H2O2 cause 1- Convert FA on cell membrane to peroxide hemolysis 2- Convert Hb to methemoglobin that lead to increase cell membrane fragility Drug that increase symptoms Child is without symptoms under normal condition but show hemolysis when exposed to 1-Fava beans 2- Antimalaria drug 3- Sulpha drug 4- Aspirin 5- All cereal  11 Blood glucose 1- Fasting blood level 70 – 110 mg/ dl 2- One hour after meal reach 120 – 150 mg/ dl Factor regulate blood glucose 1- Hormonal regulation Insulin (role of insulin in carbohydrate metabolism) Insulin secreted from β cell of pancreas, it ↓ blood glucose by the following 1- Transfer glucose into cell 2- Stimulation of glycolysis through activation of hexokinase, PFK1, pyruvate kinase 3- Stimulation of glycogenesis 4- Inhibition of glycogenolysis 5- Inhibition of gluconeogenesis 6- Stimulation of lipogenesis (transfer of glucose into lipid ) 7- Stimulation of protein synthesis (transfer of glucose into protein ) Anti-insulin hormone 1- Glucagon Secreted from α cell of pancreas ↑ blood glucose by the following Stimulation of glycogenolysis Stimulation of gluconeogenesis 2- Catecholamine (epinephrine and nor epinephrine) Stimulation of glycogenolysis Inhibit glucose uptake by liver 3- Corticosteroid (glucocorticoid) Stimulation of gluconeogenesis Inhibit glucose uptake by tissue 4- Growth hormone Inhibit glucose uptake, ↓ insulin hormone 5- Thyroid hormone ↓ insulin hormone, Stimulation of glycogenolysis  12 2- Hepatic regulation During fasting Liver make glycogenolysis & gluconeogenesis After meal Liver make glycogenesis & lipogenesis 3- Renal regulation Renal threshold Its blood glucose above which (180 mg/ dl ) glucose appear in urine 1- Abnormal low renal threshold (100 mg/ dl ) called diabetes innocence Glucose appear in urine even insulin is normal due 220 High threshold to kidney disease occur in 25% in pregnancy Nomal threshold 2- Abnormal high renal threshold (220 mg/ dl ) 180 Glucose not appear in urine even the patient is diabetic 100 Low threshold Occur in old person 70 0 1H 2H Variation in blood glucose 1- Hyperglycemia 2- ↑ blood glucose above normal - Fasting more than 126 mg/ dl 1 H after meal more than 200 mg/ dl Cause 1- ↓ insulin as in Diabetes mellitus Surgical removal of pancreas 2- ↑ Anti Insulin hormone A- Adrenaline Stress , emotion B- Cortisone as drug C- Thyroid Hyperthyrodism D- growth hormone Giagantism  13 Hypoglycemia ↓ Blood glucose below 40 mg/ dl Its more dangerous than hyperglycemia because brain depend on glucose Symptoms 1- Confusion , dizziness 2- Tremors , weakness, tachycardia 3- If not managed lead to coma Causes 1- ↑ insulin as in A- Excessive dose of insulin during TTT of DM B- Missed meal during TTT with insulin C- Insulinoma is tumor in pancreas secrete excess insulin 2- ↓ Anti Insulin hormone A- Glucocorticoid as in Addison syndrome B- Pituitary hormone as in hypothyrodism 3- Glycogen storage disease as Von Jerkes 4- Fructosemia & galactosemia Diabetes mellitus Definition: Its hyperglycemia and glucosuria Types Type I Type II Other name Insulin dependant Non insulin dependant diabetes mellitus diabetes mellitus Age During childhood After 35 years Nutritional state Usually under weight Usually obese Hereditary state Autoimmune Moderate Plasma insulin Low or absent May be normal Oral drug Has no effect Effective TTT with insulin Always necessary May not required Complication More common Less common (ketosis )  14 Manifestation of diabetes mellitus 1- Carbohydrate metabolism A- ↓ insulin ↓ glucose uptake by cell ↓ glucose in cell polyphagia (excessive eating ) B- Hyperglycemia due to ↓ glucose oxidation and ↑ gluconeogenesis ↑ blood osmolarity which take water from tissue dehydration polydepsia (excessive drink) C- Glucosuria due to hyperglycemia excess glucose in urine osmotic diuresis polyurea excessive micturition D-Excessive loss of water soluble vitamin 2- Protein metabolism A- ↓ insulin ↑ protein catabolism ↑ gluconeogenesis B- ↑ protein catabolism from muscle muscle wasting C- ↓ Antibody formation ↓ resistance ↑ infection D- Poor healing of wound 3- Lipid metabolism A- ↓ insulin ↑ lipolysis in adipose tissues lead to 1- Loss of weight 2- Storage of fat in the liver fatty liver B- ↑ Fatty acid oxidation ↑ acetyl Co A ↑ ketone bodies and cholesterol C- Hypercholestrolemia and atherosclerosis 4- Microangiopathy Means degeneration of small blood vessel A- Retinopathy affect retina blindness B- Nephropathy affect kidney renal failure Most frequent symptoms of diabetes 1- Polyphagia 2- Polyurea 3- Polydepsia  15 Difference between hypo and hyperglycemic coma Hyperglycemic Hypoglycemic coma coma 1- Odour Acetone odour in No odour 2- nose 3- Dehydration Present (dry skin, Absent sunken eye) 4- Pulse Normal Rabid & weak 5- 6- History DM Injection of insulin 7- TTT Injection of insulin Injection of glucose and K Diagnosis of D.M 1- Glucose tolerance curve Normal Impaired DM Fasting ‹ 110 110 - 125 › 126 1 H after ‹ 140 › 140 -200 › 200 meal Oral glucose tolerance test (OGTT) Glucose tolerance is the ability of body to utilize glucose without appearance of glucose in urine How the curve is done 1- The patient come fasting 12 H 2- The fasting blood sugar measured and urine tested for glucose 3- Then patient taken 50 – 100 gm glucose ( 1 gm / kg) 4- Then blood sugar is taken every ½ h for 2 or 3 h and the urine tested  16 Result 1- Normal glucose tolerance test A- Fasting level 70 – 110 mg / dl B- After 1 H blood glucose rises to reach 180 renal threshold 120 – 150 mg/dl due to glucose absorption C- After 2 H blood glucose return to fasting 150 Level due to utilization of glucose by insulin D- Urine sample contain no glucose 70 70 0 1h 2h 2- Curve of diabetes mellitus A- Fasting blood sugar severe In moderate 160 mg/ dl moderate In severe 190 mg/ dl 190 B- After 1 H renal threshold In moderate ESI substrate Ex. Glugokinase inhibited by P Enzyme Inhibitor Kinetic effect of non Competitive inhibitors on Vmax and Km V max is decrease Km constant Effect of Line weaver Burk Blot Vmax 1 Vmax 2  71 Km EI ES 1/Vmax 1/Vmax -1/Km Isoenzyme Definition They are isomer of the same enzyme have the same catalytic activity but differ in physical, molecular weight, and electrophoretic mobility Ex. 1- Lactic dehydrogenase (LDH) Pyruvic Lactic dehydrogenase (1,2,3,4,5) Lactic acid LD is formed of 4 subunit (tetramer) formed of different proportion of H (heart) & M (muscle) LDH isoenzyme Subunit LD1 HHHH (Heart) LD2 HHHM LD3 HHMM LD4 HMMM LD5 MMMM (synthesis in liver, stored in muscle) Clinical importance of LD LD1,2 increase in heart disease (myocardial infarction) LD 3 increase in acute leukemia LD 5 increase in liver disease (hepatities) 2- Creatine phospho kinase (CPK) It convert creatine CPK creatine phosphate CPK is dimer formed of 2 subunit CPK BB present in brain (↑ in brain damage) CPK MB present in heart (↑ in myocardial infarction) CPK MM present in muscle (↑ in muscle atrophy)